Orally administered Lactobacillus strains differentially affect the direction and efficacy of the immune response

In mice, strain dependent cytokine production profiles are induced after oral administration of Lactobacillus. Such a cytokine profile seems to determine the direction and efficacy of the humoral response. In SJL mice lactobacilli are able to enhance or inhibit the development of disease after induction of experimental autoimmune encephalomyelitis (EAE). Immuno- histochemical analysis of cytokine profiles showed that differential modulation is obtained dependent on the Lactobacillus strain applied. Serum antibody responses to i.p. immunisation with chicken gama globulin in BALB/c mice are also modulated by oral application of Lactobacillus. Lactobacilli are now being developed as safe live antigen carriers for application in vaccine technology, but also for the excretion of autoantigens in order to induce tolerance. The findings of this study imply that by proper strain selection the direction of the response can be influenced by the induction of a specific cytokine profile

Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in oral tolerance induction for intervention in an autoimmune disease, multiple sclerosis. Recombinant L. casei which express surface-anchored tetanus toxin fragment C (TTFC) were generated. Quantitative analysis by flow cytometry demonstrated a high level of cell wall-bound expression of TTFC and immunogenicity was demonstrated by parenteral immunization with whole cell extracts of the recombinants. A series of expression vectors was constructed to secrete human myelin basic protein (hMBP) or hMBP as a fusion protein with β-glucuronidase from Escherichia coli. These heterologous products produced by L. casei were detected in the growth medium and parenteral immunization with this medium evoked antibodies against hMBP, confirming that secretion indeed had occurred. Based on the different localization of the heterologous proteins, lactobacilli expressing surface-anchored TTFC are ideally suited for the induction of antibody responses, whereas lactobacilli that secrete myelin proteins can be used for the induction of peripheral T-cell tolerance. In conclusion, the specific technology described here allows the construction of a wide array of safe live recombinant lactobacilli which may prove to be useful in oral intervention strategies for the prevention of infectious diseases or treatment of autoimmune diseases